Poster presented at the 25th EADV Congress, Vienna, Austria, 28 September – 2 October 2016 Calcipotriol plus betamethasone dipropionate foam is effective in patients with moderate-to-severe psoriasis: post-hoc analysis of the PSO-ABLE study Carle Paul,1 Craig Leonardi,2 Alan Menter,3 Kristian Reich,4 Linda Stein Gold,5 Richard B Warren,6 Anders Møller,7 Mark Lebwohl8 1Paul Sabatier University and Larrey Hospital, Toulouse, France; 2St Louis University School of Medicine, St Louis, MO, USA; 3Baylor University Medical Center, Dallas, TX, USA; 4Dermatologikum Hamburg and SCIderm GmbH, Hamburg, Germany; 5Henry Ford Health System, Detroit, MI, USA; 6Dermatology Centre, University of Manchester, Manchester, UK; 7LEO Pharma A/S, Ballerup, Denmark; 8Icahn School of Medicine at Mount Sinai, New York, NY, USA Introduction ● Most guidelines recommend that mild-to-moderate psoriasis be treated with topical therapies.1,2 Use of topical therapies in severe/extensive psoriasis is not generally recommended ● Ointment and gel formulations of fixed combination calcipotriol 50 μg/g (Cal) plus betamethasone 0.5 mg/g (BD) are established first-line topical treatments.3 A foam formulation has been developed with the aim of enhancing adherence and increasing the therapeutic options available ● Studies with Cal/BD foam have demonstrated greater in vitro drug penetration and a greater antipsoriatic effect over 4 weeks of treatment than Cal/BD ointment and vehicle, with a comparable tolerability profile4–7 ● The Phase III PSO-ABLE study (NCT02132936) in patients with mild-to-severe psoriasis demonstrated that Cal/BD foam had superior efficacy at week 4 compared with Cal/BD gel at week 8 (based on the recommended treatment periods in the approved labels)8 ● This analysis from PSO-ABLE assesses the efficacy of Cal/BD foam and gel in the subgroup of patients with moderate-to-severe psoriasis Materials and methods PSO-ABLE STUDY DESIGN ● Prospective, multicentre, investigator-blinded ● Patients were randomized 4:4:1:1 to once-daily Cal/BD foam, Cal/BD gel, foam vehicle or gel vehicle for up to 12 weeks8 PATIENTS ● Aged ≥18 years with mild-to-severe psoriasis according to the physician’s global assessment of disease severity (PGA), involving 2–30% body surface area (BSA), and a modified (excluding the head, which was not treated) Psoriasis Area and Severity Index (mPASI) of ≥2 ● For inclusion in this subgroup analysis, a patient was required to have ‘moderate-to-severe’ psoriasis based on the ‘Rule of Tens’9: – BSA affected ≥10% or mPASI score >10 or Dermatology Life Quality Index (DLQI) score >10 ASSESSMENTS AND ENDPOINTS ● Efficacy was assessed at weeks 4, 8 and 12 by calculating: – Proportion of patients achieving a ≥75% or ≥90% reduction in mPASI – Change from baseline in BSA affected – Proportion of patients who were clear/almost clear of psoriasis, with a ≥2 grade improvement according to PGA (defined as ‘treatment success’) ● Patients completed the DLQI questionnaire at baseline and weeks 4, 8 and 12 (range 0–30). Quality of life was assessed by calculating the proportion of patients achieving: – DLQI score of 0/1 (ie no impact of psoriasis on the patient’s life) – Decrease in DLQI score of ≥5 (ie the minimal clinically important difference) ● The amount of each product used throughout the study was also assessed STATISTICAL ANALYSIS ● Analyses were conducted on the full analysis set, which comprised all patients with moderate-to-severe psoriasis ● Last observation carried forward (LOCF) was used to impute values for missing mPASI data. An observed case approach was used for other variables ● This subgroup analysis demonstrates that Cal/BD foam is effective in patients with moderate-to-severe psoriasis; it should be noted however, that it is difficult to treat psoriasis patients who have large BSA involvement purely with topical therapy. The superior efficacy of Cal/BD foam over Cal/BD gel that was observed in the primary PSO-ABLE study was maintained for up to 12 weeks 8 in these patients ● Potential limitations of this analysis: the definition of moderate-to-severe (based on the ‘Rule of Tens’9) differs from that used in studies of systemic therapies, where patients are typically required to have BSA ≥10% and PASI >10; mean BSA, mPASI score and DLQI scores in this study were close to 10, therefore on the threshold for moderate-to-severe psoriasis ● This subanalysis suggests Cal/BD foam may be a cost- saving alternative to systemic therapies, in some patients with moderate-to-severe psoriasis who are able to maintain adherence to topical therapy and do not want to be exposed to systemic therapy Conclusions Results PATIENTS ● 463 patients were randomized to Cal/BD foam (n=185), Cal/BD gel (n=188), foam vehicle (n=47) and gel vehicle (n=43) Seventy-seven Cal/BD foam patients and 82 Cal/BD gel patients – were classified as having moderate-to-severe psoriasis (Table 1) Acknowledgements This study was sponsored by LEO Pharma. Medical writing support was provided by Andrew Jones, PhD, from Mudskipper Business Ltd, funded by LEO Pharma References 1. Menter A et al. J Am Acad Dermatol 2009;60:643–659. 2. Nast A et al. Arch Dermatol Res 2012;304:87–113. 3. Laws PM & Young HS. Expert Opin Pharmacother 2010;11:1999–2009. 4. Hollesen Basse L et al. J Invest Dermatol 2014;134:S33:abst 192. 5. Koo J et al. J Dermatolog Treat 2016;27:120–127. 6. Leonardi C et al. J Drugs Dermatol 2015;14:1468–1477. 7. Queille-Roussel C et al. Clin Drug Investig 2015;35:239–245. 8. Paul C et al. J Eur Acad Dermatol Venereol 2016;in press. 9. Finlay AY. Br J Dermatol 2005;152:861–867. 60 (a) (b) 50 40 20 30 10 0 Week 4 Week 8 Week 12 Cal/BD foam (n=77) Cal/BD gel (n=82) Pa ti en ts a ch ie vi ng m PA SI 75 (% ) 30 25 15 20 10 5 0 Week 4 Week 8 Week 12 Pa ti en ts a ch ie vi ng m PA SI 90 (% ) 40.3 17.1 53.2 22.0 57.1 35.4 11.7 2.4 27.3 8.5 15.6 12.2 Figure 1. Proportion of patients with moderate-to-severe psoriasis achieving (a) mPASI75 and (b) mPASI90 (LOCF) 100 80 60 40 20 0 Baseline Week 4 Week 8 Week 12 n=77Cal/BD foam n=75 n=73 n=71 n=82Cal/BD gel Cal/BD foam Cal/BD gel n=79 n=77 n=76 Ch an ge in B SA a � ec te d (% ) Figure 2. Reduction in BSA affected by psoriasis from baseline in moderate-to-severe patients (observed cases) 40 35 30 20 25 10 15 5 0 Week 4 Week 8 Week 12 Cal/BD foam Cal/BD gel Pa ti en ts a ch ie vi ng tr ea tm en t s uc ce ss (% ) n=75 n=79 n=73 n=77 n=71 n=76 32.0 19.0 35.6 16.9 38.0 31.6 Figure 3. Proportion of moderate-to-severe patients achieving treatment success during treatment (observed cases) 60 50 40 20 30 10 0 Week 4 Week 8 Week12 Cal/BD foam Cal/BD gel Pa ti en ts a ch ie vi ng D LQ I s co re of 0 o r 1 (% ) n=74 n=78 n=73 n=74 n=70 n=76 33.8 14.1 42.5 28.4 55.7 29.3 Figure 4. Proportion of patients achieving a DLQI score of 0/1 (observed cases) Table 1. Patient demographics and disease characteristics at baseline Cal/BD foam (n=77) Cal/BD gel (n=82) Males:females, n 49:28 47:35 Age, years 53.2 ± 12.9 52.1 ± 14.8 BSA, % 10.9 ± 6.8 10.4 ± 6.4 mPASI score 10.2 ± 5.2 8.9 ± 4.0 DLQI score 10.4 ± 5.7 12.0 ± 6.4 Note: All data are mean ± standard deviation (SD) mPASI SCORES ● The proportion of patients achieving mPASI75 and mPASI90 was greater with Cal/BD foam than Cal/BD gel at weeks 4, 8 and 12 (Figure 1) – Percentage mean (± SD) reduction in mPASI from baseline to week 12 was 66.8 ± 37.6% with Cal/BD foam and 57.7 ± 34.4% with Cal/BD gel BSA AFFECTED BY PSORIASIS ● The proportion of BSA affected decreased throughout treatment in both Cal/BD foam and Cal/BD gel groups (Figure 2) – Percentage mean (± SD) reduction from baseline to week 12 was 50.2 ± 43.0% with Cal/BD foam and 39.2 ± 37.7% for Cal/BD gel TREATMENT SUCCESS ● Treatment success rates increased throughout the first 6 weeks, reaching 32.0% by week 4 in the Cal/BD foam group; these rates continued to increase up to week 12 (Figure 3) Success rates were higher with Cal/BD foam than Cal/BD gel at – each time point DLQI SCORES ● A greater proportion of patients achieved a DLQI of 0/1 at weeks 4, 8 and 12 with Cal/BD foam than Cal/BD gel (Figure 4) ● The proportion of patients achieving a decrease in DLQI of ≥5 with Cal/BD foam was greater than with Cal/BD gel at week 4 (70.3% vs 56.4%), then similar at weeks 8 (68.5% vs 66.2%) and 12 (62.9% vs 64.0%) AMOUNT OF PRODUCT USED ● The mean amount of Cal/BD foam used was 28.0 ± 20.3 g/week, compared with 22.6 ± 18.1 g/week of Cal/BD gel The greatest usage of Cal/BD foam occurred in the first 6 weeks– pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2 pcg-workstation-2 Sticky Note Marked set by pcg-workstation-2